MEDICAL AND NON-MEDICAL TESTOSTERONE AND STEROID HORMONE USAGE AMANDA HO, MD

DISCLOSURES

I have no relevant financial interests to disclose.

LEARNING OBJECTIVES

Explain the different effects of testosterone on men and women.

Compare different steroid hormone testing options.

Describe ways in which testing of hormones differs from testing for other analytes.

Explain the ways in which anabolic steroid usage for athletic performance differs from medical usage of testosterone therapy.

TESTOSTERONE

DEFINITIONS

Hormone: a small molecule produced by an endocrine gland that acts on other cells

Growth and development

Homeostasis

Energy usage

Steroid hormone: a fat-soluble hormone with four fused rings in its structure

Other types of hormones: proteins and amino acid derivatives

Hormones

Steroids Proteins Amino acids

STEROID HORMONES

Fat-soluble

Can pass through cell membranes

Act on nuclear receptors

Affect gene expression

Act more slowly than protein or amino acid hormones

T

T

ANDROGENS

Hormones that develop and maintain male secondary sexual characteristics

Hormones

Steroids

Corticosteroids

Glucocorticoids

Mineralocorticoids

Sex steroids

Androgens

Estrogens

Progestogens

Proteins Amino acids

Made out of cholesterol

Precursors: DHEA, androstenedione

95% is made in Leydig cells in the testes

Remaining 5% is made peripherally

Circulate through the blood bound to transport proteins

TESTOSTERONE IN CIRCULATION

Albumin SHBG SHBG

T

T

T

T

T

T

T

TOTAL FREE

CONCENTRATIONS - MALE

Three peaks in the male life cycle: 2nd trimester of fetal development

2-3 months of age

Puberty (reaches a plateau) – 300-1080 ng/dL

Starting around age 40, testosterone levels decline by 0.5-2%/year Decrease in number of Leydig cells

Decrease in the GnRH pulse amplitude

CONCENTRATIONS - FEMALE

9-55 ng/dL

Made in the ovaries and the adrenal glands

No fetal or neonatal peak

Does increase at puberty

Diurnal variation

Total testosterone peaks slightly before ovulation

Seems to decrease with menopause

Figure 2. Mean serum total and free testosterone and LH levels during the normal menstrual cycle in 34 healthy women. Data are the mean ± sd.

Published in: Indrani Sinha-Hikim; Stefan Arver; Gildon Beall; Ruoqing Shen; Mario Guerrero; Fred Sattler; Cecilia Shikuma; Jerald C. Nelson; Britt-Marie Landgren; Norman A. Mazer; Shalender Bhasin; The Journal of Clinical Endocrinology & Metabolism 1998, 83, 1312-1318. DOI: 10.1210/jcem.83.4.4718 Copyright © 1998

CONCENTRATIONS

REGULATION: HYPOTHALAMIC-PITUITARY-GONADAL AXIS

Hypothalamus

Anterior pituitary gland Gonads

Gonadotropin-releasing hormone (GnRH)

Luteinizing hormone (LH), follicle-stimulating hormone (FSH)

Testosterone, inhibin

EFFECTS ON THE BODY

Affects cells that are sensitive to androgens

Male sexual characteristics

Acne

Erythropoiesis

Increased lean body mass

Increased energy and libido

HOW WE TEST FOR TESTOSTERONE

CLIENT QUESTION

My patient is receiving testosterone injections.

What test do I order to measure testosterone?

SOME OF THE QUESTIONS THAT NEED TO BE ANSWERED

Man, woman, or child?

Expected levels?

Total, free, or bioavailable?

MEN VS WOMEN AND CHILDREN

Men: 300-1080 ng/dL

Women and children: as low as 1 ng/dL

Electrochemiluminescent immunoassay vs HPLC-MS/MS

Analytical sensitivity:

Immunoassay: 3 ng/dL, but imprecise

HPLC-MS/MS: 1.0 ng/dL

TOTAL, FREE, OR BIOAVAILABLE?

Total: measures all testosterone

Free

Bound to SHBG

Bound to albumin

Free: unbound, dissolved in blood

Either calculated or measured directly with equilibrium dialysis

Bioavailable: free + albumin-bound

Calculated

MEASURING SHBG

Quantitative electrochemiluminescent immunoassay

Helps to determine free vs bound testosterone

Many conditions may affect SHBG and thus affect total testosterone

FACTORS AFFECTING SHBG

Decrease

Obesity

Hypothyroidism

Diabetes

Glucocorticoids and progestins

Androgenic steroids

Increase

Aging

Liver disease

Hyperthyroidism

HIV

Estrogens

Anti-seizure medications

PITFALLS OF STEROID HORMONE TESTING

Present in small amounts

Bound to carrier molecules

Diurnal variation

TESTING CONSIDERATIONS

Gender and age

Expected levels – in concordance with patient’s gender and age?

Need more information than a total level?

MEDICAL TESTOSTERONE THERAPY

ACCORDING TO THE FDA…

Testosterone replacement therapy should only be given to men with confirmed low levels of testosterone and symptoms of testosterone deficiency

SYMPTOMS OF ANDROGEN DEFICIENCY

Nonspecific

Decreased energy

Depression

Anemia

Reduced muscle bulk and strength

Diminished performance

Specific

Decreased libido

Loss of body hair

Low bone mineral density or low-trauma fracture

Hot flushes

Infertility

Small testicular size

HYPOGONADISM

Primary

Disease of the testes

High GnRH, FSH, LH

Acquired or congenital

Secondary

Disease of the hypothalamus or pituitary

Low GnRH, FSH, LH

Acquired or congenital

AGE-RELATED DECREASE IN TESTOSTERONE

Remember, testosterone decreases by 0.5-2%/year

Only problematic when symptomatic

Many names:

Testosterone deficiency syndrome (TDS)

Late-onset hypogonadism (LOH)

(Partial) androgen deficiency of the aging male ((P)ADAM)

Goal: to improve signs and symptoms of deficiency

LAB DIAGNOSIS

Endocrine Society Clinical Practice Guideline (Bhasin S et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59.):

Don’t screen everybody

Measure morning testosterone levels twice

If borderline low, consider testing free or SHBG

MALE CONTRACEPTION

Testosterone inhibits production of LH and FSH

The testes need FSH in order to produce sperm

Hypothalamus

Anterior pituitary gland Gonads

Gonadotropin-releasing hormone (GnRH)

Luteinizing hormone (LH), follicle-stimulating hormone (FSH)

Testosterone, inhibin

FEMALE TO MALE TRANSITION

Hormone therapy is one part of the overall gender transition in transgender patients

Two goals of hormone therapy in transitioning from female to male: Suppress native (female) hormones

Induce and maintain male secondary sexual characteristics

FEMALE TO MALE TRANSITION: EFFECTS OF TESTOSTERONE ADMINISTRATION

What changes

Facial hair growth

Deepening of the voice

Increase in lean body mass

Acne

Increased libido

Breast changes

Susceptibility to male pattern baldness

Cessation of menstruation

What stays the same

Female bone structure

Shorter height

Broader hips

Breast fat mass

Genitalia

FORMULATIONS

Oral?

Almost completely metabolized in first pass

Intramuscular injection

Gel, cream, or patch

Intradermal implant

Nasal spray

Buccal patch

MONITORING RECOMMENDATIONS

Endocrine Society Clinical Practice Guideline (Bhasin S et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59.):

Measure serum testosterone 3-6 months after starting supplementation and then annually

Goal is to achieve a total serum testosterone level in the middle of the normal range for a young, healthy adult male (300-1000 ng/dL)

ADVERSE EFFECTS

May increase risk of cardiovascular disease

May worsen symptoms of BPH

May increase risk of prostate cancer

Probably increases hematocrit

Acne

Gynecomastia

Suppression of spermatogenesis

NON-MEDICAL TESTOSTERONE USAGE

ANABOLIC STEROIDS

ANDROGENIC ANABOLIC STEROIDS

Hormones that have the same biological effects as testosterone

We’ve discussed the androgenic (masculinizing) effects of testosterone

Also anabolic (muscle-building) effects

Synthetic hormones designed to have more anabolic than androgenic effects

DO THEY WORK?

Hard to determine, because often used in supratherapeutic doses

Lean body mass increase of 2-5kg

Increase in circumference of shoulders, neck, upper arms

Increase in muscle strength

ADVERSE EFFECTS

Hard to determine, because often used in supratherapeutic doses

Suppression of HPG axis Decreased sperm production and testicular atrophy

Increased aggression and hostility

Acne

Gynecomastia

REGULATION

Over 630 sports agencies follow the guidelines of the World Anti-Doping Agency (WADA) International Olympics Committee (IOC)

Major US sports leagues have their own policies

WADA DOCUMENTS

Prohibited Substances

Int’l Standard for Therapeutic Use Exemptions

Int’l Standard for Protection of Privacy

Int’l Standard for Testing and Investigation

Int’l Standard for Laboratories

BANNED AAS

Exogenous AAS, and other substances with a similar chemical structure or similar biological effect(s).

Endogenous AAS, when administered exogenously, and their metabolites and isomers.

MEASURING ANABOLIC STEROIDS

Tests available to measure many different anabolic steroids in the urine

Testosterone to epitestosterone ratio

Testosterone to LH ratio

Creatinine

Masking agents

IN SUMMARY

Testosterone is present in both men and women and exerts similar masculinizing effects on both

Choosing a lab test to measure testosterone depends on the demographics of the patient and expected levels

Steroid hormone levels change throughout the day and throughout the lifespan

FDA recommends administration to a small group

There are many possible side effects of exogenous administration

Positive and negative effects of anabolic steroids are difficult to measure

THANK YOU!